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https://www.readbyqxmd.com/read/27913309/sequence-determinants-of-the-caenhorhabditis-elegansdopamine-transporter-dictating-in-vivoaxonal-export-and-synaptic-localization
#1
Sarah B Robinson, J Andrew Hardaway, Shannon L Hardie, Jane Wright, Ryan M Glynn, Daniel P Bermingham, Qiao Han, Sarah M Sturgeon, Phyllis Freeman, Randy D Blakely
The monoamine neurotransmitter dopamine (DA) acts across phylogeny to modulate both simple and complex behaviors. The presynaptic DA transporter (DAT) is a major determinant of DA signaling capacity in ensuring efficient extracellular DA clearance. In humans, DAT is also a major target for prescribed and abused psychostimulants. Multiple structural determinants of DAT function and regulation have been defined, though largely these findings have arisen from heterologous expression or ex vivo cell culture studies...
November 29, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27912243/vomeronasal-receptors-in-vertebrates-and-the-evolution-of-pheromone-detection
#2
Liliana Silva, Agostinho Antunes
Pheromones were identified as chemical signals used for intraspecific communication in insects (e.g., sexual attraction) in the 1950s. However, only almost 40 years later the vomeronasal receptors type-1 (V1R) and type-2 (V2R) were identified, usually associated with the presence of a vomeronasal organ (VNO). VRs are widespread in amphibians, reptiles, and mammals, but birds lost the VNO. Similarly, fishes lack VRs and a VNO but can still detect pheromones, instead using the olfactory receptors related to class A and class C G protein-coupled receptors...
November 28, 2016: Annual Review of Animal Biosciences
https://www.readbyqxmd.com/read/27911814/distinct-cortical-and-striatal-actions-of-a-%C3%AE-arrestin-biased-dopamine-d2-receptor-ligand-reveal-unique-antipsychotic-like-properties
#3
Nikhil M Urs, Steven M Gee, Thomas F Pack, John D McCorvy, Tama Evron, Joshua C Snyder, Xiaobao Yang, Ramona M Rodriguiz, Emiliana Borrelli, William C Wetsel, Jian Jin, Bryan L Roth, Patricio O'Donnell, Marc G Caron
The current dopamine (DA) hypothesis of schizophrenia postulates striatal hyperdopaminergia and cortical hypodopaminergia. Although partial agonists at DA D2 receptors (D2Rs), like aripiprazole, were developed to simultaneously target both phenomena, they do not effectively improve cortical dysfunction. In this study, we investigate the potential for newly developed β-arrestin2 (βarr2)-biased D2R partial agonists to simultaneously target hyper- and hypodopaminergia. Using neuron-specific βarr2-KO mice, we show that the antipsychotic-like effects of a βarr2-biased D2R ligand are driven through both striatal antagonism and cortical agonism of D2R-βarr2 signaling...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27909990/orexin-hypocretin-signaling
#4
Jyrki P Kukkonen
Orexin/hypocretin peptide (orexin-A and orexin-B) signaling is believed to take place via the two G-protein-coupled receptors (GPCRs), named OX1 and OX2 orexin receptors, as described in the previous chapters. Signaling of orexin peptides has been investigated in diverse endogenously orexin receptor-expressing cells - mainly neurons but also other types of cells - and in recombinant cells expressing the receptors in a heterologous manner. Findings in the different systems are partially convergent but also indicate cellular background-specific signaling...
December 2, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27909248/regulation-of-chemokine-receptor-ccr2-recycling-by-filamin-a-phosphorylation
#5
Mònica Pons, Ismael Izquierdo, Mireia Andreu-Carbó, Georgina Garrido, Jesús Planagumà, Olivia Muriel, M Isabel Geli, Anna M Aragay
Proper endosomal trafficking of ligand-activated G protein-coupled receptors (GPCRs) is essential to spatiotemporally tune their physiological responses. For the monocyte chemoattractant receptor 2 (CCR2B), endocytic recycling is important to sustain monocyte migration; while filamin A (FLNa) is essential for CCL2-induced monocyte migration. Here, we analyze the role of FLNa in the trafficking of CCR2B along the endocytic pathway. In FLNa knockdown cells, activated CCR2B accumulated in enlarged EEA-1-positive endosomes, which exhibited slow movement and fast fluorescence recovery, suggesting an imbalance between receptor entry and exit rates...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27909152/involvement-of-mesolimbic-dopaminergic-network-in-neuropathic-pain-relief-by-treadmill-exercise-a-study-for-specific-neural-control-with-gi-dreadd-in-mice
#6
Kenta Wakaizumi, Takashige Kondo, Yusuke Hamada, Michiko Narita, Rui Kawabe, Hiroki Narita, Moe Watanabe, Shigeki Kato, Emiko Senba, Kazuto Kobayashi, Naoko Kuzumaki, Akihiro Yamanaka, Hiroshi Morisaki, Minoru Narita
BACKGROUND: Exercise alleviates pain and it is a central component of treatment strategy for chronic pain in clinical setting. However, little is known about mechanism of this exercise-induced hypoalgesia. The mesolimbic dopaminergic network plays a role in positive emotions to rewards including motivation and pleasure. Pain negatively modulates these emotions, but appropriate exercise is considered to activate the dopaminergic network. We investigated possible involvement of this network as a mechanism of exercise-induced hypoalgesia...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27908837/angiotensin-type-1a-receptor-regulates-%C3%AE-arrestin-binding-of-the-%C3%AE-2-adrenergic-receptor-via-heterodimerization
#7
András D Tóth, Pál Gyombolai, Bence Szalai, Péter Várnai, Gábor Turu, László Hunyady
Heterodimerization between angiotensin type 1A receptor (AT1R) and β2-adrenergic receptor (β2AR) has been shown to modulate G protein-mediated effects of these receptors. Activation of G protein-coupled receptors (GPCRs) leads to β-arrestin binding, desensitization, internalization and G protein-independent signaling of GPCRs. Our aim was to study the effect of heterodimerization on β-arrestin coupling. We found that β-arrestin binding of β2AR is affected by activation of AT1Rs. Costimulation with angiotensin II and isoproterenol markedly enhanced the interaction between β2AR and β-arrestins, by prolonging the lifespan of β2AR-induced β-arrestin2 clusters at the plasma membrane...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27908726/activation-of-g-protein-coupled-estrogen-receptor-1-improves-early-onset-cognitive-impairment-via-pi3k-akt-pathway-in-rats-with-traumatic-brain-injury
#8
Ze-Fen Wang, Zhi-Yong Pan, Cheng-Shi Xu, Zhi-Qiang Li
Previous studies experimentally reveal that G-protein coupled estrogen receptor 1(GPER) has neuroprotection against ischemic injury. However, its effect on traumatic brain injury (TBI) is less well-established. Cognitive impairment following human TBI is a common clinical observation, and TBI is considered as a risk factor for Alzheimer's disease (AD). This study aimed to observe the possible protective effect of GPER on early-onset cognitive impairment after a single TBI and investigate the cellular mechanism underlying its actions...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27908653/molecular-changes-in-children-with-heart-failure-undergoing-left-ventricular-assist-device-therapy
#9
Elizabeth Medina, Carmen C Sucharov, Penny Nelson, Shelley D Miyamoto, Brian L Stauffer
OBJECTIVE: To determine whether left ventricular assist device (LVAD) treatment in children with heart failure would result in the modification of molecular pathways involved in heart failure pathophysiology. STUDY DESIGN: Forty-seven explanted hearts from children were studied (16 nonfailing control, 20 failing, and 11 failing post-LVAD implantation [F-LVAD]). Protein expression and phosphorylation states were determined by receptor binding assays and Western blots...
November 29, 2016: Journal of Pediatrics
https://www.readbyqxmd.com/read/27907116/rnai-mediated-functional-analysis-of-bursicon-genes-related-to-adult-cuticle-formation-and-tanning-in-the-honeybee-apis-mellifera
#10
Claudinéia Pereira Costa, Moysés Elias-Neto, Tiago Falcon, Rodrigo Pires Dallacqua, Juliana Ramos Martins, Marcia Maria Gentile Bitondi
Bursicon is a heterodimeric neurohormone that acts through a G protein-coupled receptor named rickets (rk), thus inducing an increase in cAMP and the activation of tyrosine hydroxylase, the rate-limiting enzyme in the cuticular tanning pathway. In insects, the role of bursicon in the post-ecdysial tanning of the adult cuticle and wing expansion is well characterized. Here we investigated the roles of the genes encoding the bursicon subunits during the adult cuticle development in the honeybee, Apis mellifera...
2016: PloS One
https://www.readbyqxmd.com/read/27906878/serum-concentrations-of-receptor-for-interleukin-8-in-patients-with-esophageal-cancer
#11
Marta Łukaszewicz-Zając, Agnieszka Kulczyńska-Przybik, Paweł Muszyński, Mirosław Kozłowski, Maciej Szmitkowski, Barbara Mroczko
INTRODUCTION A specific receptor for interleukin 8, known as C-X-C chemokine type‑2 receptor (CXCR‑2), is one of the 7‑transmembrane G‑protein‑coupled receptors. Its involvement in the development of numerous malignancies, including esophageal cancer (EC), has been suggested. OBJECTIVES The aim of this study was to assess the diagnostic and prognostic usefulness of serum CXCR‑2 level measurement in patients with EC, in comparison with C‑reactive protein (CRP) levels and classic tumor markers such as carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC‑Ag)...
October 18, 2016: Polskie Archiwum Medycyny Wewnętrznej
https://www.readbyqxmd.com/read/27906555/ligand-biased-regulation-of-ptdins-3-4-5-p3-dependent-signal-transduction-in-gpcr-control-of-pituitary-hormone-release
#12
Joshua G Pemberton, John P Chang
Biased signaling describes the selective activation of signal transduction cascades by structurally-related ligands downstream of shared G protein-coupled receptors (GPCRs). Although class I phosphoinositide 3-kinases (PI3Ks) are important components of GPCR-controlled transduction networks, little is known regarding the potential for biased regulation of class I PI3K-dependent signaling. The full compliment of class I PI3K catalytic subunits (p110α, p110β, p110δ and p110γ) first appear in bony fishes and, despite being associated with distinct cellular functions, all class I PI3Ks produce the lipid second-messenger phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3)...
December 1, 2016: Endocrinology
https://www.readbyqxmd.com/read/27905542/defining-an-olfactory-receptor-function-in-airway-smooth-muscle-cells
#13
William H Aisenberg, Jessie Huang, Wanqu Zhu, Premraj Rajkumar, Randy Cruz, Lakshmi Santhanam, Niranjana Natarajan, Hwan Mee Yong, Breann De Santiago, Jung Jin Oh, A-Rum Yoon, Reynold A Panettieri, Oliver Homann, John K Sullivan, Stephen B Liggett, Jennifer L Pluznick, Steven S An
Pathways that control, or can be exploited to alter, the increase in airway smooth muscle (ASM) mass and cellular remodeling that occur in asthma are not well defined. Here we report the expression of odorant receptors (ORs) belonging to the superfamily of G-protein coupled receptors (GPCRs), as well as the canonical olfaction machinery (Golf and AC3) in the smooth muscle of human bronchi. In primary cultures of isolated human ASM, we identified mRNA expression for multiple ORs. Strikingly, OR51E2 was the most highly enriched OR transcript mapped to the human olfactome in lung-resident cells...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905440/organization-and-functions-of-mglu-and-gabab-receptor-complexes
#14
Jean-Philippe Pin, Bernhard Bettler
The neurotransmitters glutamate and γ-aminobutyric acid (GABA) transmit synaptic signals by activating fast-acting ligand-gated ion channels and more slowly acting G-protein-coupled receptors (GPCRs). The GPCRs for these neurotransmitters, metabotropic glutamate (mGlu) and GABAB receptors, are atypical GPCRs with a large extracellular domain and a mandatory dimeric structure. Recent studies have revealed how these receptors are activated through multiple allosteric interactions between subunit domains. It emerges that the molecular complexity of these receptors is further increased through association with trafficking, effector and regulatory proteins...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27905105/endothelin-1-et-1-stimulates-carboxy-terminal-smad2-phosphorylation-in-vascular-endothelial-cells-by-a-mechanism-dependent-on-et-receptors-and-de-novo-protein-synthesis
#15
Narges Sharifat, Ghorban Mohammad Zadeh, Mohammad-Ali Ghaffari, Parisa Dayati, Danielle Kamato, Peter J Little, Hossein Babaahmadi-Rezaei
OBJECTIVE: G protein-coupled receptor (GPCR) agonists through their receptors can transactivate protein tyrosine kinase receptors such as epidermal growth factor receptor and serine/threonine kinase receptors most notably transforming growth factor (TGF)-β receptor (TβRI). This signalling mechanism represents a major expansion in the cellular outcomes attributable to GPCR signalling. This study addressed the role and mechanisms involved in GPCR agonist, endothelin-1 (ET-1)-mediated transactivation of the TβRI in bovine aortic endothelial cells (BAECs)...
December 1, 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27904774/the-g-protein-coupled-chemoattractant-receptor-fpr2-promotes-malignant-phenotype-of-human-colon-cancer-cells
#16
Yi Xiang, Xiaohong Yao, Keqiang Chen, Xiafei Wang, Jiamin Zhou, Wanghua Gong, Teizo Yoshimura, Jiaqiang Huang, Rongquan Wang, Yuzhang Wu, Guochao Shi, Xiuwu Bian, Jiming Wang
The G-protein coupled chemoattractant receptor formylpeptide receptor-2 (FPR2 in human, Fpr2 in mice) is expressed by mouse colon epithelial cells and plays a critical role in mediating mucosal homeostasis and inflammatory responses. However, the biological role of FPR2 in human colon is unclear. Our investigation revealed that a considerable number of human colon cancer cell lines expressed FPR2 and its ligands promoted cell migration and proliferation. Human colon cancer cell lines expressing high levels of FPR2 also formed more rapidly growing tumors in immunocompromised mice as compared with cell lines expressing lower levels of FPR2...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903512/thyroid-hormone-stimulated-increases-in-pgc-1%C3%AE-and-ucp2-promote-life-history-specific-endocrine-changes-and-maintain-a-lipid-based-metabolism
#17
Bridget Martinez, José G Soñanez-Organis, Jose A Godoy-Lugo, Lillian Horin, Daniel E Crocker, Rudy M Ortiz
Thyroid hormones (TH) regulate metabolism, but are typically suppressed during times of stressful physiological conditions, including fasting. Interestingly, prolonged fasting in northern elephant seal pups is associated with reliance on a lipid-based metabolism and increased levels of circulating thyroid hormones that are partially attributed to active secretion as opposed to reduced clearance. This apparent paradox is coupled with complementary increases in cellular TH-mediated activity suggesting that in mammals naturally adapted to prolonged fasting TH are necessary to support metabolism...
November 30, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27901063/regulation-of-%C3%AE-2b-adrenergic-receptor-cell-surface-transport-by-gga1-and-gga2
#18
Maoxiang Zhang, Wei Huang, Jie Gao, Alvin V Terry, Guangyu Wu
The molecular mechanisms that control the targeting of newly synthesized G protein-coupled receptors (GPCRs) to the functional destinations remain poorly elucidated. Here, we have determined the role of Golgi-localized, γ-adaptin ear domain homology, ADP ribosylation factor-binding proteins 1 and 2 (GGA1 and GGA2) in the cell surface transport of α2B-adrenergic receptor (α2B-AR), a prototypic GPCR, and studied the underlying mechanisms. We demonstrated that knockdown of GGA1 and GGA2 by shRNA and siRNA significantly reduced the cell surface expression of inducibly expressed α2B-AR and arrested the receptor in the perinuclear region...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899324/understanding-the-common-themes-and-diverse-roles-of-the-second-extracellular-loop-ecl2-of-the-gpcr-super-family
#19
Michael J Woolley, Alex C Conner
The extracellular loops (ECLs) of G protein-coupled receptors (GPCRs) can bind directly to docked orthosteric or allosteric ligands, they can contain transient contact points for ligand entry into the transmembrane (TM) bundle and they can regulate the activation of the receptor signalling pathways. Of the three ECLs, ECL2 is the largest and most structurally diverse reflecting its functional importance. This has been shown through biochemical techniques and has been supported by the many subsequent crystal structures of GPCRs bound to both agonists and antagonists...
November 26, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27898723/pth1r-mutants-found-in-patients-with-primary-failure-of-tooth-eruption-disrupt-g-protein-signaling
#20
Hariharan Subramanian, Frank Döring, Sina Kollert, Natalia Rukoyatkina, Julia Sturm, Stepan Gambaryan, Angelika Stellzig-Eisenhauer, Philipp Meyer-Marcotty, Martin Eigenthaler, Erhard Wischmeyer
AIM: Primary failure of tooth eruption (PFE) is causally linked to heterozygous mutations of the parathyroid hormone receptor (PTH1R) gene. The mutants described so far lead to exchange of amino acids or truncation of the protein that may result in structural changes of the expressed PTH1R. However, functional effects of these mutations have not been investigated yet. MATERIALS AND METHODS: In HEK293 cells, PTH1R wild type was co-transfected with selected PTH1R mutants identified in patients with PFE...
2016: PloS One
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